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The circumsporozoite protein (CSP) builds up the surface coat of sporozoites and is the leading malaria pre-erythrocytic-stage vaccine candidate. CSP has been shown to induce robust CD8+ T cell responses that are capable of eliminating developing parasites in hepatocytes resulting in protective immunity. In this study, we characterised the importance of the immunodominant CSP-derived epitope, SYIPSAEKI, of Plasmodium berghei in both sporozoite- and vaccine-induced protection in murine infection models. In BALB/c mice, where SYIPSAEKI is efficiently presented in the context of the major histocompatibility complex class I (MHC-I) molecule H-2-Kd, we established that epitope-specific CD8+ T cell responses contribute to parasite killing following sporozoite immunisation. Yet, sterile protection was achieved in the absence of this epitope substantiating the concept that other antigens can be sufficient for parasite-induced protective immunity. Furthermore, we demonstrated that SYIPSAEKI-specific CD8+ T cell responses elicited by viral-vectored CSP-expressing vaccines effectively targeted parasites in hepatocytes. The resulting sterile protection strictly relied on the expression of SYIPSAEKI. In C57BL/6 mice, which are unable to present the immunodominant epitope, CSP-based vaccines did not confer complete protection, despite the induction of high levels of CSP-specific antibodies. These findings underscore the significance of CSP in protection against malaria pre-erythrocytic stages and demonstrate that a significant proportion of the protection against the parasite is mediated by CD8+ T cells specific for the immunodominant CSP-derived epitope.

This is a case of adult-onset autoimmune enteropathy (AIE) in a 46-year-old man with multiple autoimmune conditions who presented with worsening disease process after receiving cyclophosphamide. We describe the investigations and management of this patient over a 6-year timeline. The diagnosis and management of AIE is challenging given the heterogeneity in clinicopathologic findings and a small number of adult case reports. We describe the current diagnostic criteria, review the literature on treatment options and outcomes, and discuss the evidence for cyclophosphamide in the treatment of AIE. Adult-onset AIE should be considered in the differential diagnosis of refractory diarrhea and weight loss.

Background Operating room (OR) metrics are frequently cited when optimizing cost efficacy and quality of care (Weiss et al, Characteristics of operating room procedures in U.S. hospitals, 2011: Statistical brief #170, 2013; Macario A, Anesthesiology 105:237-240, 2006; Childers et al, JAMA Surg 153:e176233, 2018). Little has been reported to evaluate how anesthesia trainees change anesthesia-related efficiencies in the OR. Statistical correlation may demonstrate awareness and implementation of efficient systems-based practice. Methods Utilizing computerized OR information systems, specific data regarding anesthesia controlled turnover times were collected (546 data points) over the course of 4 months. The type of surgery performed, patient’s American Society of Anesthesiologists (ASA) physical status and OR turnover times were compared for clinical anesthesia (CA) trainee levels CA1, CA2, CA3 and CRNAs. Standard descriptive statistics were computed. Analysis of variance (ANOVA) was performed to compare the average turnover time. Results Average OR turnover time was 31 min ranging from 8 to 60 min. There was a significant difference between the OR turnover time of CA-1 (32 min) compared to CA-3 (29 min) (p = 0.017) and CA-1 compared to CRNA (30 min) (p = 0.016). OR turnover time was significantly shorter in CA-3 and CRNA. The analysis showed no differences between OR turnover time of ASA categories. Conclusions These findings posit that trainees improve efficiency over time, but that education may for a time come at the expense of productivity. This trend may demonstrate a more profound understanding and mastery of a learner progressing in the graduate medical education system. This interplay plays a key role in clinical and academic shared success.